AC430 is a potent and specific small molecule inhibitor of janus kinase 2 (JAK2), which has been implicated as a target for therapy in both oncology and autoimmune disease.
Role of JAK2 in Oncology. JAK2 is a kinase that plays an important role during the maturation and differentiation of hematopoietic cells. The V617F mutation in JAK2 is found in a majority of patients with myeloproliferative disease.
Role of JAK2 in Immuno-Inflammatory Diseases.Aberrant cytokine signaling through JAK2 can promote autoimmune and inflammatory responses, and several inhibitors of this pathway have demonstrated promising efficacy in early clinical trials.
AC430 Development.AC430 was specifically developed to be a best-in-class JAK2 inhibitor. In preclinical studies, AC430 has exhibited potency against JAK2 and V617F mutated JAK2 in cell-based models that is at least equivalent to, and in most cases superior to, competing JAK2 inhibitors. In preclinical oncology and autoimmune models, AC430 is well tolerated and has significant efficacy at oral doses as low as 10 mg/kg/day. IND-enabling studies with AC430, including 28-day toxicology studies in monkeys and rats, indicate that AC430 is well tolerated at significant multiples of doses exhibiting efficacy, given orally once-a-day. An IND for AC430 was filed in September 2010 and a Phase 1 clinical trial in healthy volunteers was initiated in the fourth quarter of 2010 to determine the safety, tolerability and pharmacokinetics of AC430 in healthy volunteers.